JP2019521189A5 - - Google Patents
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- JP2019521189A5 JP2019521189A5 JP2019520930A JP2019520930A JP2019521189A5 JP 2019521189 A5 JP2019521189 A5 JP 2019521189A5 JP 2019520930 A JP2019520930 A JP 2019520930A JP 2019520930 A JP2019520930 A JP 2019520930A JP 2019521189 A5 JP2019521189 A5 JP 2019521189A5
- Authority
- JP
- Japan
- Prior art keywords
- carbonyl
- group
- fluoro
- trifluoromethyl
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 238000009472 formulation Methods 0.000 claims 60
- 239000000203 mixture Substances 0.000 claims 60
- 238000001356 surgical procedure Methods 0.000 claims 22
- 125000001424 substituent group Chemical group 0.000 claims 17
- 229910052799 carbon Inorganic materials 0.000 claims 14
- -1 cyano, carboxyl Chemical group 0.000 claims 12
- 125000004429 atom Chemical group 0.000 claims 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims 10
- 125000000623 heterocyclic group Chemical group 0.000 claims 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 10
- 238000002360 preparation method Methods 0.000 claims 10
- 125000005843 halogen group Chemical group 0.000 claims 8
- 229910052757 nitrogen Inorganic materials 0.000 claims 8
- BIUDHHGROGJSHN-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)benzaldehyde Chemical group FC1=CC=C(C=O)C=C1C(F)(F)F BIUDHHGROGJSHN-UHFFFAOYSA-N 0.000 claims 7
- 229910052739 hydrogen Inorganic materials 0.000 claims 7
- 239000001257 hydrogen Substances 0.000 claims 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
- 229910052760 oxygen Inorganic materials 0.000 claims 7
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 6
- 125000002619 bicyclic group Chemical group 0.000 claims 6
- 125000004122 cyclic group Chemical group 0.000 claims 6
- 229910052717 sulfur Inorganic materials 0.000 claims 6
- 229940123524 TRPA1 antagonist Drugs 0.000 claims 5
- 238000011200 topical administration Methods 0.000 claims 5
- 206010061218 Inflammation Diseases 0.000 claims 4
- 208000002193 Pain Diseases 0.000 claims 4
- 125000003118 aryl group Chemical group 0.000 claims 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 230000004054 inflammatory process Effects 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 239000002562 thickening agent Substances 0.000 claims 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 3
- 150000001875 compounds Chemical class 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 210000002919 epithelial cell Anatomy 0.000 claims 3
- 229910017053 inorganic salt Inorganic materials 0.000 claims 3
- 239000002736 nonionic surfactant Substances 0.000 claims 3
- 230000003287 optical effect Effects 0.000 claims 3
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
- JOPCBOLOBMEUNK-UHFFFAOYSA-N 1'-[1-[4-fluoro-3-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]-6-(trifluoromethyl)spiro[1H-3,1-benzoxazine-4,4'-piperidine]-2-one Chemical compound FC1=C(C=C(C=C1)N1N=C(C=C1C=1C=NC=CC=1)C(=O)N1CCC2(CC1)OC(NC1=C2C=C(C=C1)C(F)(F)F)=O)C(F)(F)F JOPCBOLOBMEUNK-UHFFFAOYSA-N 0.000 claims 2
- DTOUUUZOYKYHEP-UHFFFAOYSA-N 1,3-bis(2-ethylhexyl)-5-methyl-1,3-diazinan-5-amine Chemical compound CCCCC(CC)CN1CN(CC(CC)CCCC)CC(C)(N)C1 DTOUUUZOYKYHEP-UHFFFAOYSA-N 0.000 claims 2
- JKXYOQDLERSFPT-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-octadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO JKXYOQDLERSFPT-UHFFFAOYSA-N 0.000 claims 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims 2
- WHAZPKNVNDEWOV-UHFFFAOYSA-N 4,5-difluoro-3-[1-[1-[4-iodo-3-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]piperidin-4-yl]-1H-benzimidazol-2-one Chemical compound FC=1C=CC2=C(N(C(N2)=O)C2CCN(CC2)C(=O)C2=NN(C(=C2)C=2C=NC=CC=2)C2=CC(=C(C=C2)I)C(F)(F)F)C=1F WHAZPKNVNDEWOV-UHFFFAOYSA-N 0.000 claims 2
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims 2
- 206010015958 Eye pain Diseases 0.000 claims 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- 239000012062 aqueous buffer Substances 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 229960004867 hexetidine Drugs 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims 2
- 239000003921 oil Substances 0.000 claims 2
- 235000019198 oils Nutrition 0.000 claims 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims 2
- 238000002271 resection Methods 0.000 claims 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 2
- 239000012929 tonicity agent Substances 0.000 claims 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims 1
- MAKMQGKJURAJEN-RUZDIDTESA-N (2r)-1-benzyl-n-(3-spiro[1h-2-benzofuran-3,4'-piperidine]-1'-ylpropyl)pyrrolidine-2-carboxamide Chemical compound C([C@@H]1C(NCCCN2CCC3(CC2)C2=CC=CC=C2CO3)=O)CCN1CC1=CC=CC=C1 MAKMQGKJURAJEN-RUZDIDTESA-N 0.000 claims 1
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 claims 1
- ZKTKBCKGLVJVBD-UHFFFAOYSA-N 1-(3,5-dichloro-4-fluorophenyl)-8-[1-[4-fluoro-3-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound ClC=1C=C(C=C(C=1F)Cl)N1CNC(C11CCN(CC1)C(=O)C1=NN(C(=C1)C=1C=NC=CC=1)C1=CC(=C(C=C1)F)C(F)(F)F)=O ZKTKBCKGLVJVBD-UHFFFAOYSA-N 0.000 claims 1
- NXPDAOKLDWMPEG-UHFFFAOYSA-N 1-(4-fluoro-3,5-dimethylphenyl)-8-[1-[3-fluoro-4-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=C(C=C(C=C1C)N1CNC(C11CCN(CC1)C(=O)C1=NN(C(=C1)C=1C=NC=CC=1)C1=CC(=C(C=C1)C(F)(F)F)F)=O)C NXPDAOKLDWMPEG-UHFFFAOYSA-N 0.000 claims 1
- NDIKNOFRWJDXNK-UHFFFAOYSA-N 1-(4-fluoro-3,5-dimethylphenyl)-8-[1-[4-fluoro-3-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=C(C=C(C=C1C)N1CNC(C11CCN(CC1)C(=O)C1=NN(C(=C1)C=1C=NC=CC=1)C1=CC(=C(C=C1)F)C(F)(F)F)=O)C NDIKNOFRWJDXNK-UHFFFAOYSA-N 0.000 claims 1
- ITJHHIJGDAYDTJ-UHFFFAOYSA-N 1-(4-fluoro-3,5-dimethylphenyl)-8-[5-pyridin-3-yl-1-(3,4,5-trifluorophenyl)pyrazole-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=C(C=C(C=C1C)N1CNC(C11CCN(CC1)C(=O)C1=NN(C(=C1)C=1C=NC=CC=1)C1=CC(=C(C(=C1)F)F)F)=O)C ITJHHIJGDAYDTJ-UHFFFAOYSA-N 0.000 claims 1
- AMHQMFAHIHSLDV-UHFFFAOYSA-N 1-(4-fluorophenyl)-8-[1-(4-iodophenyl)-5-pyridin-3-ylpyrazole-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=CC=C(C=C1)N1CNC(C11CCN(CC1)C(=O)C1=NN(C(=C1)C=1C=NC=CC=1)C1=CC=C(C=C1)I)=O AMHQMFAHIHSLDV-UHFFFAOYSA-N 0.000 claims 1
- RYDXXBHXVKCOMT-UHFFFAOYSA-N 1-(4-fluorophenyl)-8-[1-[4-fluoro-3-(trifluoromethyl)phenyl]-4,5-dihydropyrazolo[3,4-f]quinoline-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=C(C=C(C=C1)N1N=C(C=2CCC3=C(C1=2)C=CC=N3)C(=O)N1CCC2(C(NCN2C2=CC=C(C=C2)F)=O)CC1)C(F)(F)F RYDXXBHXVKCOMT-UHFFFAOYSA-N 0.000 claims 1
- MUJMKXOXWOMVFG-UHFFFAOYSA-N 1-(4-fluorophenyl)-8-[1-[4-fluoro-3-(trifluoromethyl)phenyl]-4,5-dihydropyrazolo[4,3-h]quinoline-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=C(C=C(C=C1)N1N=C(C=2CCC3=C(C1=2)N=CC=C3)C(=O)N1CCC2(C(NCN2C2=CC=C(C=C2)F)=O)CC1)C(F)(F)F MUJMKXOXWOMVFG-UHFFFAOYSA-N 0.000 claims 1
- VTVJQPMBNOJAEO-UHFFFAOYSA-N 1-(4-fluorophenyl)-8-[1-[4-fluoro-3-(trifluoromethyl)phenyl]-5-pyrazin-2-ylpyrazole-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=C(C=C(C=C1)N1N=C(C=C1C1=NC=CN=C1)C(=O)N1CCC2(C(NCN2C2=CC=C(C=C2)F)=O)CC1)C(F)(F)F VTVJQPMBNOJAEO-UHFFFAOYSA-N 0.000 claims 1
- ZZPNNIGVCYGDIY-UHFFFAOYSA-N 1-(4-fluorophenyl)-8-[1-[4-fluoro-3-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=C(C=C(C=C1)N1N=C(C=C1C=1C=NC=CC=1)C(=O)N1CCC2(C(NCN2C2=CC=C(C=C2)F)=O)CC1)C(F)(F)F ZZPNNIGVCYGDIY-UHFFFAOYSA-N 0.000 claims 1
- QDQJNZZUKSXSQJ-UHFFFAOYSA-N 1-(4-fluorophenyl)-8-[1-[4-iodo-3-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound FC1=CC=C(C=C1)N1CNC(C11CCN(CC1)C(=O)C1=NN(C(=C1)C=1C=NC=CC=1)C1=CC(=C(C=C1)I)C(F)(F)F)=O QDQJNZZUKSXSQJ-UHFFFAOYSA-N 0.000 claims 1
- VAZJLPXFVQHDFB-UHFFFAOYSA-N 1-(diaminomethylidene)-2-hexylguanidine Polymers CCCCCCN=C(N)N=C(N)N VAZJLPXFVQHDFB-UHFFFAOYSA-N 0.000 claims 1
- SAPAJGANEIAYNX-UHFFFAOYSA-N 1-[1-[1-[3-fluoro-4-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]piperidin-4-yl]-2-oxo-3H-benzimidazole-5-carbonitrile Chemical compound FC=1C=C(C=CC=1C(F)(F)F)N1N=C(C=C1C=1C=NC=CC=1)C(=O)N1CCC(CC1)N1C(NC2=C1C=CC(=C2)C#N)=O SAPAJGANEIAYNX-UHFFFAOYSA-N 0.000 claims 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 claims 1
- POAOYUHQDCAZBD-UHFFFAOYSA-N 2-butoxyethanol Chemical compound CCCCOCCO POAOYUHQDCAZBD-UHFFFAOYSA-N 0.000 claims 1
- SSGODOUBZYHZPI-UHFFFAOYSA-N 2-fluoro-4-[3-[1'-(4-fluorophenyl)-4'-oxospiro[8-azabicyclo[3.2.1]octane-3,5'-imidazolidine]-8-carbonyl]-5-pyridin-3-ylpyrazol-1-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)N1N=C(C=C1C=1C=NC=CC=1)C(=O)N1C2CC3(N(CNC3=O)C3=CC=C(C=C3)F)CC1CC2 SSGODOUBZYHZPI-UHFFFAOYSA-N 0.000 claims 1
- FZIPCQLKPTZZIM-UHFFFAOYSA-N 2-oxidanylpropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O FZIPCQLKPTZZIM-UHFFFAOYSA-N 0.000 claims 1
- HDVLYVAMDRPDAJ-UHFFFAOYSA-N 3-[1-[1-[2,3-difluoro-4-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]piperidin-4-yl]-4,5-difluoro-1H-benzimidazol-2-one Chemical compound FC1=C(C=CC(=C1F)C(F)(F)F)N1N=C(C=C1C=1C=NC=CC=1)C(=O)N1CCC(CC1)N1C(NC2=C1C(=C(C=C2)F)F)=O HDVLYVAMDRPDAJ-UHFFFAOYSA-N 0.000 claims 1
- NAMSANQPIIFYFB-UHFFFAOYSA-N 3-[1-[1-[2,4-difluoro-3-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]piperidin-4-yl]-4,5-difluoro-1H-benzimidazol-2-one Chemical compound FC1=C(C=CC(=C1C(F)(F)F)F)N1N=C(C=C1C=1C=NC=CC=1)C(=O)N1CCC(CC1)N1C(NC2=C1C(=C(C=C2)F)F)=O NAMSANQPIIFYFB-UHFFFAOYSA-N 0.000 claims 1
- RAYXTBBGHGNIGB-UHFFFAOYSA-N 3-[1-[1-[2,5-difluoro-4-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]piperidin-4-yl]-4,5-difluoro-1H-benzimidazol-2-one Chemical compound FC1=C(C=C(C(=C1)C(F)(F)F)F)N1N=C(C=C1C=1C=NC=CC=1)C(=O)N1CCC(CC1)N1C(NC2=C1C(=C(C=C2)F)F)=O RAYXTBBGHGNIGB-UHFFFAOYSA-N 0.000 claims 1
- BSDKBHZUTNDWJU-UHFFFAOYSA-N 3-[1-[1-[4-chloro-3-(trifluoromethyl)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]piperidin-4-yl]-4,5-difluoro-1H-benzimidazol-2-one Chemical compound ClC1=C(C=C(C=C1)N1N=C(C=C1C=1C=NC=CC=1)C(=O)N1CCC(CC1)N1C(NC2=C1C(=C(C=C2)F)F)=O)C(F)(F)F BSDKBHZUTNDWJU-UHFFFAOYSA-N 0.000 claims 1
- IFEITTVRIWOATK-UHFFFAOYSA-N 3-[1-[4-bromo-5-pyridin-3-yl-1-(3,4,5-trifluorophenyl)pyrazole-3-carbonyl]piperidin-4-yl]-4,5-difluoro-1H-benzimidazol-2-one Chemical compound BrC=1C(=NN(C=1C=1C=NC=CC=1)C1=CC(=C(C(=C1)F)F)F)C(=O)N1CCC(CC1)N1C(NC2=C1C(=C(C=C2)F)F)=O IFEITTVRIWOATK-UHFFFAOYSA-N 0.000 claims 1
- JLRADJYECXRWJF-UHFFFAOYSA-N 3-[1-[5-(1-benzylimidazol-4-yl)-1-[4-fluoro-3-(trifluoromethyl)phenyl]pyrazole-3-carbonyl]piperidin-4-yl]-4,5-difluoro-1H-benzimidazol-2-one Chemical compound C(C1=CC=CC=C1)N1C=NC(=C1)C1=CC(=NN1C1=CC(=C(C=C1)F)C(F)(F)F)C(=O)N1CCC(CC1)N1C(NC2=C1C(=C(C=C2)F)F)=O JLRADJYECXRWJF-UHFFFAOYSA-N 0.000 claims 1
- IHDPXOBJCHYLMX-UHFFFAOYSA-N 3-[1-[5-(2-chloropyridin-3-yl)-1-[3-fluoro-4-(trifluoromethyl)phenyl]pyrazole-3-carbonyl]piperidin-4-yl]-4,5-difluoro-1H-benzimidazol-2-one Chemical compound ClC1=NC=CC=C1C1=CC(=NN1C1=CC(=C(C=C1)C(F)(F)F)F)C(=O)N1CCC(CC1)N1C(NC2=C1C(=C(C=C2)F)F)=O IHDPXOBJCHYLMX-UHFFFAOYSA-N 0.000 claims 1
- FRFPHRYOGAKFQJ-UHFFFAOYSA-N 3-[1-[5-(6-chloropyridin-3-yl)-1-[3-fluoro-4-(trifluoromethyl)phenyl]pyrazole-3-carbonyl]piperidin-4-yl]-4,5-difluoro-1H-benzimidazol-2-one Chemical compound ClC1=CC=C(C=N1)C1=CC(=NN1C1=CC(=C(C=C1)C(F)(F)F)F)C(=O)N1CCC(CC1)N1C(NC2=C1C(=C(C=C2)F)F)=O FRFPHRYOGAKFQJ-UHFFFAOYSA-N 0.000 claims 1
- KVRGTYAMRKDANJ-UHFFFAOYSA-N 4,5-difluoro-3-[1-[1-(4-iodophenyl)-5-pyridin-3-ylpyrazole-3-carbonyl]piperidin-4-yl]-1H-benzimidazol-2-one Chemical compound FC=1C=CC2=C(N(C(N2)=O)C2CCN(CC2)C(=O)C2=NN(C(=C2)C=2C=NC=CC=2)C2=CC=C(C=C2)I)C=1F KVRGTYAMRKDANJ-UHFFFAOYSA-N 0.000 claims 1
- XPHVDEFJZKIAMG-UHFFFAOYSA-N 4,5-difluoro-3-[1-[1-[2-methyl-4-(trifluoromethoxy)phenyl]-5-pyridin-3-ylpyrazole-3-carbonyl]piperidin-4-yl]-1H-benzimidazol-2-one Chemical compound FC=1C=CC2=C(N(C(N2)=O)C2CCN(CC2)C(=O)C2=NN(C(=C2)C=2C=NC=CC=2)C2=C(C=C(C=C2)OC(F)(F)F)C)C=1F XPHVDEFJZKIAMG-UHFFFAOYSA-N 0.000 claims 1
- NJXNGZVSAFYEOV-UHFFFAOYSA-N 4,5-difluoro-3-[1-[1-[3-fluoro-4-(trifluoromethyl)phenyl]-5-(4-methylpyridin-3-yl)pyrazole-3-carbonyl]piperidin-4-yl]-1H-benzimidazol-2-one Chemical compound CC1=C(C=NC=C1)C1=CC(=NN1C1=CC(F)=C(C=C1)C(F)(F)F)C(=O)N1CCC(CC1)N1C(=O)NC2=C1C(F)=C(F)C=C2 NJXNGZVSAFYEOV-UHFFFAOYSA-N 0.000 claims 1
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| PCT/US2017/040976 WO2018009717A1 (en) | 2016-07-06 | 2017-07-06 | Trpa1 antagonists for treatment of dry eye, ocular pain and inflammation |
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| SG11201605559VA (en) | 2014-01-06 | 2016-08-30 | Algomedix Inc | Trpa1 modulators |
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| US12220396B2 (en) | 2019-05-03 | 2025-02-11 | Zyus Life Sciences Inc. | Formulation for pain management |
| US12178797B2 (en) | 2019-05-03 | 2024-12-31 | Zyus Life Sciences Inc. | Formulation for pain management |
| AU2020268218B2 (en) * | 2019-05-03 | 2022-09-08 | Zyus Life Sciences Inc. | Formulation for pain management |
| GR1010012B (el) * | 2020-05-12 | 2021-05-27 | Φαρματεν Α.Β.Ε.Ε. | Φαρμακευτικο σκευασμα ελευθερο συντηρητικου για οφθαλμικη χορηγηση περιεχον κυκλοσπορινη |
| IT202100015098A1 (it) | 2021-06-09 | 2022-12-09 | Flonext S R L | Composto antagonista del canale trpa1 per uso in patologie degenerative della retina |
| CA3224809A1 (en) * | 2021-07-12 | 2023-01-19 | Paramita SARKAR | Skin moisturizing compositions |
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| EP1620095A4 (en) * | 2003-04-24 | 2009-04-01 | Merck & Co Inc | HEMMER OF ACT ACTIVITY |
| SG11201605559VA (en) * | 2014-01-06 | 2016-08-30 | Algomedix Inc | Trpa1 modulators |
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